PHLPP2 Downregulation Contributes to Lung Carcinogenesis Following B[a]P/B[a]PDE Exposure

Huang, Haishan; Pan, Xiaofu; Jin, Honglei; Li, Yang; Zhang, Lin; Yang, Caili; Liu, Pei; Liu, Ya; Chen, Lili; Li, Jingxia; Zhu, Junlan; Zeng, Xingruo; Fu, Kai; Chen, Guorong; Gao, Jimin; Huang, Chuanshu

doi:10.1158/1078-0432.ccr-14-2829

Cited by 53 publications

(44 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Importantly, compared with the air-liquid interface cell exposure (ALICE) system, submerged culture system is more suitable for modeling chronic exposure (Herzog et al 2014), as the oil pollutants exposure scenario in our study. We did not use KGM but used DMEM as the culture medium because we carefully followed the culture medium condition (DMEM) that was previously reported for studying exposure-induced malignant transformation of the BEAS-2B cells (Huang et al 2015; Kim et al 2015; Liu et al 2014; Park et al 2015; Son et al 2012; Stueckle et al 2012). In addition, numerous studies (e.g., (Dieudonne et al 2012; Jahn et al 2000; Kaur et al 2008; Skuland et al 2014)) have used BEAS-2B cells cultured in DMEM as a model for airway epithelium.…”

Section: Discussionmentioning

confidence: 99%

The impact of oil spill to lung health—Insights from an RNA-seq study of human airway epithelial cells

Liu

Roy-Engel

Baddoo

et al. 2016

Gene

View full text Add to dashboard Cite

The Deepwater Horizon oil spill (BP oil spill) in the Gulf of Mexico was a unique disaster event, where a huge amount of oil spilled from the sea bed and a large volume of dispersants were applied to clean the spill. The operation lasted for almost three months and involved >50,000 workers. The potential health hazards to these workers may be significant as previous research suggested an association of persistent respiratory symptoms with exposure to oil and oil dispersants. To reveal the potential effects of oil and oil dispersants on the respiratory system at the molecular level, we evaluated the transcriptomic profile of human airway epithelial cells grown under treatment of crude oil, the dispersants Corexit 9500 and Corexit 9527 and oil-dispersant mixtures. We identified a very strong effect of Corexit 9500 treatment, with 84 genes (response genes) differentially expressed in treatment vs. control samples. We discovered an interactive effect of oil-dispersant mixtures; while no response gene was found for Corexit 9527 treatment alone, cells treated with Corexit 9527 + oil mixture showed an increased number of response genes (46 response genes), suggesting a synergic effect of 9527 with oil on airway epithelial cells. Through GO (gene ontology) functional term and pathway-based analysis, we identified upregulation of gene sets involved in angiogenesis and immune responses and downregulation of § Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript gene sets involved in cell junctions and steroid synthesis as the prevailing transcriptomic signatures in the cells treated with Corexit 9500, oil or Corexit 9500 + oil mixture. Interestingly, these key molecular signatures coincide with important pathological features observed in common lung diseases, such as asthma, cystic fibrosis and chronic obstructive pulmonary disease. Our study provides mechanistic insights into the detrimental effects of oil and oil dispersants to the respiratory system and suggests significant health impacts of the recent BP oil spill to those people involved in the cleaning operation.

show abstract

Section: Discussionmentioning

confidence: 99%

The impact of oil spill to lung health—Insights from an RNA-seq study of human airway epithelial cells

Liu

Roy-Engel

Baddoo

et al. 2016

Gene

View full text Add to dashboard Cite

show abstract

“…Adjacent normal lung tissue specimens were taken from a standard distance (3 cm) from the margin of resected neoplastic tissues of patients with tumors who endured surgical lung ablation. Specimens were examined by pathologists, 37 and then frozen at −80°C until shipment on dry ice. The protein extracts were prepared using the same protocol for mouse lung tissues, and then subjected to western blot for determination of SQSTM1 expression.…”

Section: Methodsmentioning

confidence: 99%

Upregulation of SQSTM1/p62 contributes to nickel-induced malignant transformation of human bronchial epithelial cells

Huang

Zhu

et al. 2016

Autophagy

Self Cite

View full text Add to dashboard Cite

Chronic lung inflammation is accepted as being associated with the development of lung cancer caused by nickel exposure. Therefore, identifying the molecular mechanisms that lead to a nickel-induced sustained inflammatory microenvironment that causes transformation of human bronchial epithelial cells is of high significance. In the current studies, we identified SQSTM1/p62 as a novel nickel-upregulated protein that is important for nickel-induced inflammatory TNF expression, subsequently resulting in transformation of human bronchial epithelial cells. We found that nickel exposure induced SQSTM1 protein upregulation in human lung epithelial cells in vitro and in mouse lung tissues in vivo. The SQSTM1 upregulation was also observed in human lung squamous cell carcinoma. Further studies revealed that the knockdown of SQSTM1 expression dramatically inhibited transformation of human lung epithelial cells upon chronic nickel exposure, whereas ectopic expression of SQSTM1 promoted such transformation. Mechanistic studies showed that the SQSTM1 upregulation by nickel was the compromised result of upregulating SQSTM1 mRNA transcription and promoting SQSTM1 protein degradation. We demonstrated that nickel-initiated SQSTM1 protein degradation is mediated by macroautophagy/autophagy via an MTOR-ULK1-BECN1 axis, whereas RELA is important for SQSTM1 transcriptional upregulation following nickel exposure. Furthermore, SQSTM1 upregulation exhibited its promotion of nickel-induced cell transformation through exerting an impetus for nickel-induced inflammatory TNF mRNA stability. Consistently, the MTOR-ULK1-BECN1 autophagic cascade acted as an inhibitory effect on nickel-induced TNF expression and cell transformation. Collectively, our results demonstrate a novel SQSTM1 regulatory network that promotes a nickel-induced tumorigenic effect in human bronchial epithelial cells, which is negatively controlled by an autophagic cascade following nickel exposure.

show abstract

“…Protein expression levels were analyzed by calculating the integrated optical density per stained area (IOD/area) using Image-Pro Plus version 6.0 (Media Cybernetics, MD, USA). More detailed procedure was described in our previous published studies (26). …”

Section: Methodsmentioning

confidence: 99%

Induction of miR-137 by Isorhapontigenin (ISO) Directly Targets Sp1 Protein Translation and Mediates Its Anticancer Activity Both In Vitro and In Vivo

Zeng

Zhou

et al. 2016

Molecular Cancer Therapeutics

Self Cite

View full text Add to dashboard Cite

Our recent studies found that isorhapontigenin (ISO) showed a significant inhibitory effect on human bladder cancer cell growth, accompanied with cell cycle G0/G1 arrest as well as down-regulation of Cyclin D1 expression at transcriptional level via inhibition of Sp1 transactivation in bladder cancer cells. In current studies, the potential ISO inhibition of bladder tumor formation has been explored in xenograft nude mouse model, and the molecular mechanisms underlying ISO inhibition of Sp1 expression and anti-cancer activities has been elucidated both in vitro and in vivo. Moreover, the studies demonstrated that ISO treatment induced the expression of miR-137, which in turn suppressed Sp1 protein translation by direct targeting Sp1 mRNA 3′UTR. Similar to ISO treatment, ectopic expression of miR-137 alone led to G0/G1 cell growth arrest and inhibition of anchorage-independent growth in human bladder cancer cells, which could be completely reversed by over-expression of GFP-Sp1. The inhibition of miR-137 expression attenuated ISO-induced the inhibition of Sp1/Cyclin D1 expression, and induction of G0/G1 cell growth arrest and suppression of cell anchorage-independent growth. Taken together, our studies have demonstrated that miR-137 induction by ISO targets Sp1 mRNA 3′UTR and inhibits Sp1 protein translation, which consequently results in reduction of Cyclin D1 expression, induction of G0/G1 growth arrest and inhibition of anchorage-independent growth in vitro and in vivo. Our results have provided novel insights into understanding the anti-cancer activity of ISO in the therapy of human bladder cancer.

show abstract

PHLPP2 Downregulation Contributes to Lung Carcinogenesis Following B[a]P/B[a]PDE Exposure

Cited by 53 publications

References 47 publications

The impact of oil spill to lung health—Insights from an RNA-seq study of human airway epithelial cells

The impact of oil spill to lung health—Insights from an RNA-seq study of human airway epithelial cells

Upregulation of SQSTM1/p62 contributes to nickel-induced malignant transformation of human bronchial epithelial cells

Induction of miR-137 by Isorhapontigenin (ISO) Directly Targets Sp1 Protein Translation and Mediates Its Anticancer Activity Both In Vitro and In Vivo

Contact Info

Product

Resources

About